Peer reviewed literature on Ambrisentan, a selective ETRA for PAH

Implications: This Circulation paper is the first peer reviewed data on the 2 pivotal Phase III trials on ambrisentan that lead the FDA to approving it for the treatment of PAH in July 2007. This paper is critically important since all new research needs to withstand the rigor of peer-review for physcians to fully embrace the findings.  And the journal Circulation is a top notch publication with "rigorous" reviewers.  Thus this publication will be well received by the PAH community and can be assimilated into the overall database of knowledge on PAH.

Analysis: This paper shows for the first time the usefulness of a selective endothelin receptor antagonist (ETRA) in PAH.  There has been great promise that selective antagonism of the endothelin A receptor may be more valuable than nonselective antagonists, but this point, of course, is controversial and can not be proven without a head to head study of these drugs (which is not planned to the best of my knowledge at least for the ETRAs on the US market).

Clearly bosentan, a nonselective ETRA, being the only FDA approved drug in this "space" until July 2007 has had the lion's share of the market in the US and abroad.  While this remains true today, ambrisentan is likely to grow in this area and the overall use of each drug, while widely debated, may well be impacted most by the overall growth in PAH itelf (with specialized PAH centers becoming the norm in large academic centers and most pharmaceutical companies doing a tremendous job in investing in educational programs in PAH for physicians outside these centers). 

Hopefully, a second ETRA in the marketplace will create additional competition and improve efficiency which will result in lower drug costs to make it easier for all patients to gain better access (which has not been a problem to date largely due to special access programs for the needy established by the pharmaceutical companies), but some specialized healthcare niches do not seem to conform to market forces (and PAH is one of them).